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4- Non-motor symptoms like constipation, depression, sleep and cognition remain major unmet needs in Parkinsons care

The rates are closer here than with nausea and vomiting

This suggests FDA labeling may include enhanced indications for: BMI 35 with history of heart attack, stroke, or coronary artery disease High-risk cardiovascular patients needing maximum weight reduction Medical Contraindications: Who Cannot Take Retatrutide Absolute Contraindications (Definite Disqualification) Personal or Family History of Medullary Thyroid Cancer: Retatrutide (like all GLP-1 medications) carries theoretical MTC risk Anyone with personal or family history cannot take it This is a black box warning that will appear on FDA label Multiple Endocrine Neoplasia Syndrome Type 2 (MEN2): Genetic condition increasing thyroid cancer risk Absolute contraindication for all GLP-1/GIP/glucagon agonists Pregnancy and Breastfeeding: Retatrutide not studied in pregnant or breastfeeding women Animal studies showed potential fetal harm Must use contraception during treatment Stop medication 2 months before attempting pregnancy Recent Bariatric Surgery: TRIUMPH trials excluded patients with bariatric surgery in past 18 months Medication may not be appropriate post-surgery Discuss timing with bariatric surgeon and endocrinologist Relative Contraindications (Case-by-Case Basis) History of Pancreatitis: GLP-1 medications may increase pancreatitis risk Prior pancreatitis = high caution Some doctors won't prescribe, others will with close monitoring Severe Gastrointestinal Disease: Gastroparesis (delayed gastric emptying) Inflammatory bowel disease (Crohn's, ulcerative colitis) Severe GERD Retatrutide slows gastric emptying could worsen these conditions Diabetic Retinopathy (for diabetics): Rapid glucose improvement can temporarily worsen retinopathy Requires ophthalmology clearance before starting Close monitoring during treatment Severe Kidney Disease: TRIUMPH trials excluded eGFR 75) may require careful consideration due to: Higher dysesthesia risk Multiple medications (drug interactions) Frailty concerns with rapid weight loss Pediatric Population: Not studied

Among them, pancreatic tumors, particularly insulinomas and pancreatic neuroendocrine tumors (pNETs), exhibit the most consistently elevated GLP-1R expression

Tirzepatide activates two hormone receptors (GLP-1 and GIP) compared to semaglutide's single GLP-1 pathway, potentially offering stronger glucose control and weight loss in combination with metformin